No abstract

Aging is associated with episodic memory decline and alterations in memory-related brain function. However, it remains unclear if age-related memory decline is associated with similar patterns of brain aging in women and men. In the current task fMRI study, we tested the hypothesis that there are sex differences in the effect of age and memory performance on brain activity during episodic encoding and retrieval of face–location associations (spatial context memory). Forty-one women and 41 men between the ages of 21 and 76 years participated in this study. Between-group multivariate partial least squares analysis of the fMRI data was conducted to directly test for sex differences and similarities in age-related and performance-related patterns of brain activity. Our behavioral analysis indicated no significant sex differences in retrieval accuracy on the fMRI tasks. In relation to performance effects, we observed similarities and differences in how retrieval accuracy related to brain activity in women and men. Both sexes activated dorsal and lateral PFC, inferior parietal cortex, and left parahippocampal gyrus at encoding, and this supported subsequent memory performance. However, there were sex differences in retrieval activity in these same regions and in lateral occipital-temporal and ventrolateral PFC. In relation to age effects, we observed sex differences in the effect of age on memory-related activity within PFC, inferior parietal cortex, parahippocampal gyrus, and lateral occipital-temporal cortices. Overall, our findings suggest that the neural correlates of age-related spatial context memory decline differ in women compared with men.

Cardiometabolic risk (CMR) factors are associated with accelerated brain aging and increased risk for sex‐dimorphic illnesses such as Alzheimer's disease (AD). Yet, it is unknown how CMRs interact with sex and apolipoprotein E‐ϵ4 (APOE4), a known genetic risk factor for AD, to influence brain age across different life stages. Using age prediction based on multi‐shell diffusion‐weighted imaging data in 21,308 UK Biobank participants, we investigated whether associations between white matter Brain Age Gap (BAG) and body mass index (BMI), waist‐to‐hip ratio (WHR), body fat percentage (BF%), and APOE4 status varied (i) between males and females, (ii) according to age at menopause in females, and (iii) across different age groups in males and females. We report sex differences in associations between BAG and all three CMRs, with stronger positive associations among males compared to females. Independent of APOE4 status, higher BAG (older brain age relative to chronological age) was associated with greater BMI, WHR, and BF% in males, whereas in females, higher BAG was associated with greater WHR, but not BMI and BF%. These divergent associations were most prominent within the oldest group of females (66–81 years), where greater BF% was linked to lower BAG. Earlier menopause transition was associated with higher BAG, but no interactions were found with CMRs. In conclusion, the findings point to sex‐ and age‐specific associations between CMRs and brain age. Incorporating sex as a factor of interest in studies addressing CMR may promote sex‐specific precision medicine, consequently improving health care for both males and females.